OBJECTIVE To sort out the evaluation mechanism and methodology of published cases of comprehensive clinical evaluation of drugs in China， and provide a reference for promoting standardized comprehensive clinical evaluation of drugs and strengthening policy transformation in China. METHODS Clinical comprehensive evaluation cases of drugs published in China from CNKI， Wanfang Data， PubMed and Web of Science were systematically searched， and the retrieval time was from the inception to December 31st， 2023. The summary and analysis were performed from the aspects of theme selection， indicator system construction， evaluation methods， comprehensive decision-making， quality control， etc. RESULTS A total of 143 pieces of literature were ultimately included from 2014 to 2023. The number of publications has shown a rapid upward trend since 2019. The subjects of the evaluation cases were mainly pediatric drugs， Chinese patent medicines， cardiovascular drugs and anti-tumor drugs. The evaluation dimensions were between 3-8， all involving safety and effectiveness dimensions. Most cases adopted rapid evaluation methods based on literature review and expert interviews/questionnaire surveys with less emphasis on real-world research. Most cases did not involve comprehensive decision-making， quality control， or policy transformation. CONCLUSIONS The clinical comprehensive evaluation of drugs in China has made rapid progress under the guidance of national policies. However， there are still issues and challenges such as incomplete evaluation methods and standards， few cases of evaluation results being converted into decision-making， and a lack of quality control mechanisms. It is suggested that standardized evaluation paths and quality control mechanisms should be explored； when the evidence-based basis is insufficient， real-world research should be conducted as much as possible， so as to accelerate the policy transformation of evaluation results.

OBJECTIVE To sort out the evaluation mechanism and methodology of published cases of comprehensive clinical evaluation of drugs in China， and provide a reference for promoting standardized comprehensive clinical evaluation of drugs and strengthening policy transformation in China. METHODS Clinical comprehensive evaluation cases of drugs published in China from CNKI， Wanfang Data， PubMed and Web of Science were systematically searched， and the retrieval time was from the inception to December 31st， 2023. The summary and analysis were performed from the aspects of theme selection， indicator system construction， evaluation methods， comprehensive decision-making， quality control， etc. RESULTS A total of 143 pieces of literature were ultimately included from 2014 to 2023. The number of publications has shown a rapid upward trend since 2019. The subjects of the evaluation cases were mainly pediatric drugs， Chinese patent medicines， cardiovascular drugs and anti-tumor drugs. The evaluation dimensions were between 3-8， all involving safety and effectiveness dimensions. Most cases adopted rapid evaluation methods based on literature review and expert interviews/questionnaire surveys with less emphasis on real-world research. Most cases did not involve comprehensive decision-making， quality control， or policy transformation. CONCLUSIONS The clinical comprehensive evaluation of drugs in China has made rapid progress under the guidance of national policies. However， there are still issues and challenges such as incomplete evaluation methods and standards， few cases of evaluation results being converted into decision-making， and a lack of quality control mechanisms. It is suggested that standardized evaluation paths and quality control mechanisms should be explored； when the evidence-based basis is insufficient， real-world research should be conducted as much as possible， so as to accelerate the policy transformation of evaluation results.

Objective:To investigate the role of serotonin reuptake transporter(SERT)and P2X3 receptor of dorsal root ganglion(DRG)in regulating visceral hypersensitivity of rats with irritable bowel syndrome(IBS)by electroacupuncture(EA). Methods:Male Sprague-Dawley and SERT-/-rats were subjected to preparing IBS visceral hypersensitivity models with 2,4,6-trinitrobenzene sulfonic acid(TNBS)enema.Three weeks post-modeling,interventions including EA,intrathecal injection,and EA plus intrathecal injection were applied,respectively.Hematoxylin-eosin staining and abdominal withdrawal reflex(AWR)score were used to confirm the successful establishment of the IBS model.AWR score,whole-cell patch clamp technique,and Western blotting assay were used to evaluate the changes in visceral pain sensitivity,electrophysiological properties of DRG neurons,and the expression of DRG P2X3 receptor and SERT in IBS rats. Results:Compared to the model group,the AWR score in the EA group decreased significantly(P<0.05),the resting membrane potential(P<0.05)and the number of action potentials(P<0.05)of DRG neurons reduced,and the baseline intensity increased(P<0.05);additionally,the expression of P2X3 receptor in DRG decreased(P<0.01),and the SERT expression increased(P<0.05).Compared to the P2X3 receptor agonist group,the SERT protein expression in DRG was higher in the EA group.In SERT-/-rats,the P2X3 receptor expression in DRG increased in the EA group compared to the model group(P<0.01). Conclusion:EA modulates the electrophysiological characteristics of intestinal primary sensory neurons by regulating the expression of SERT and P2X3 receptor in DRG of IBS rats.This modulation may contribute to the mechanism by which EA alleviates peripheral sensitization of visceral pain in IBS rats.

Objective:To investigate the effects of Schisandrin A on the proliferation and apoptosis of prostate cancer cell and its mechanism.Methods:Human prostate cancer DU145 cell were cultured in vitro and grouped into DU145 group (normal culture), Schisandrin A L group (50 μmol/L Schisandrin A was added), Schisandrin A M group (100 μmol/L Schisandrin A was added), Schisandrin A H group (150 μmol/L Schisandrin A was added) and Simvastatin group (50 μmol/L Simvastatin was added). Cell morphology of each group was observed under microscope, cell proliferation ability was detected by CCK8 method, cell migration ability was detected by cell scratch assay, cell invasion ability was detected by Transwell assay, and cell apoptosis was detected by flow cytometry, the expression of phosphorylation (p) - mammalian STE20-like protein kinase 1 (MST1), MST1, p-large tumor suppressor 1 (LATS1), LATS1, p-Yes associated protein (YAP) and YAP protein were detected by Western blotting. Measurement data were expressed as mean± standard deviation ( ± s), one-way ANOVA for comparisons between multiple groups, and t-test for comparisons between two groups. Results:Compared with DU145 group, the number of cells in Schisandrin A L, M, H groups and Simvastatin group decreased, and the cells gradually shrunk and the spacing became larger, the cell survival rate [(100.00±0.00)%, (88.41±9.36)%, (62.34±7.31)%, (42.57±5.01)%, (45.47±5.65)%], migration [(90.11±13.43)%, (74.16±8.08)%, (57.53±7.34)%, (41.34±6.79)%, (43.44±5.26)%] and invasion [(89.01±10.31)%, (73.11±9.23)%, (55.62±7.67)%, (41.13±6.35)%, (40.36±5.68)%], and the expression of p-YAP/YAP protein (0.98±0.08, 0.83±0.11, 0.69±0.07, 0.55±0.07, 0.53±0.05) were significantly decreased, the apoptosis rate [(2.88±0.34)%, (5.20±0.57)%, (8.37±0.94)%, (12.71±1.58)%, (12.03±2.21)%] and the expression of p-MST1/MST1 (0.41±0.04, 0.53±0.07, 0.75±0.07, 0.89±0.08, 0.88±0.07] and p-LATS1/LATS1 protein (0.40±0.04, 0.52±0.06, 0.64±0.06, 0.77±0.08, 0.79±0.08) were significantly increased, and the differences were statistically significant ( P<0.05). Conclusion:Schisandrin A may inhibit the proliferation of prostate cancer cell and promote cell apoptosis by inhibiting Hippo-YAP signaling pathway.

Purpose::Vibrio vulnificus ( V. Vulnificus) infection is characterized by rapid onset, aggressive progression, and challenging treatment. Bacterial resistance poses a significant challenge for clinical anti-infection treatment and is thus the subject of research. Enhancing host infection tolerance represents a novel infection prevention strategy to improve patient survival. Our team initially identified cytochrome P4501A1 (CYP1A1) as an important target owing to its negative modulation of the body's infection tolerance. This study explored the superior effects of the CYP1A1 inhibitor bergamottin compared to antibiotic combination therapy on the survival of mice infected with multidrug-resistant V. Vulnificus and the protection of their vital organs. Methods::An increasing concentration gradient method was used to induce multidrug-resistant V. Vulnificus development. We established a lethal infection model in C57BL/6J male mice and evaluated the effect of bergamottin on mouse survival. A mild infection model was established in C57BL/6J male mice, and the serum levels of creatinine, urea nitrogen, aspartate aminotransferase, and alanine aminotransferase were determined using enzyme-linked immunosorbent assay to evaluate the effect of bergamottin on liver and kidney function. The morphological changes induced in the presence of bergamottin in mouse organs were evaluated by hematoxylin and eosin staining of liver and kidney tissues. The bacterial growth curve and organ load determination were used to evaluate whether bergamottin has a direct antibacterial effect on multidrug-resistant V. Vulnificus. Quantification of inflammatory factors in serum by enzyme-linked immunosorbent assay and the expression levels of inflammatory factors in liver and kidney tissues by real-time quantitative polymerase chain reaction were performed to evaluate the effect of bergamottin on inflammatory factor levels. Western blot analysis of IκBα, phosphorylated IκBα, p65, and phosphorylated p65 protein expression in liver and kidney tissues and in human hepatocellular carcinomas-2 and human kidney-2 cell lines was used to evaluate the effect of bergamottin on the nuclear factor kappa-B signaling pathway. One-way ANOVA and Kaplan-Meier analysis were used for statistical analysis. Results::In mice infected with multidrug-resistant V. Vulnificus, bergamottin prolonged survival ( p = 0.014), reduced the serum creatinine ( p = 0.002), urea nitrogen ( p = 0.030), aspartate aminotransferase ( p = 0.029), and alanine aminotransferase ( p = 0.003) levels, and protected the cellular morphology of liver and kidney tissues. Bergamottin inhibited interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α expression in serum (IL-1β: p = 0.010, IL-6: p = 0.029, TNF-α: p = 0.025) and inhibited the protein expression of the inflammatory factors IL-1β, IL-6, TNF-α in liver (IL-1β: p = 0.010, IL-6: p = 0.011, TNF-α: p = 0.037) and kidney (IL-1β: p = 0.016, IL-6: p = 0.011, TNF-α: p = 0.008) tissues. Bergamottin did not affect the proliferation of multidrug-resistant V. Vulnificus or the bacterial load in the mouse peritoneal lavage fluid ( p = 0.225), liver ( p = 0.186), or kidney ( p = 0.637). Conclusion::Bergamottin enhances the tolerance of mice to multidrug-resistant V. Vulnificus infection. This study can serve as a reference and guide the development of novel clinical treatment strategies for V. Vulnificus.

OBJECTIVE: To investigate the clinical characteristics, prognostic factors and efficacy of hypomethylating agent (HMA) in patients with chronic myelomonocytic leukemia (CMML). METHODS: The clinical data of 37 newly diagnosed patients with CMML was analyzed retrospectively, and their clinical characteristics and the efficacy of HMA were summarized. Kaplan-Meier and Log-rank test were used for univariate survival analysis, and Cox proportional hazards regression model was used for multivariate analysis. RESULTS: The median age at diagnosis was 67 years old. Their common manifestations included fatigue, bleeding, abnormal blood routine and fever. Most patients had splenomegaly. According to FAB classification, there were 6 cases of myelodysplastic CMML and 31 cases of myeloproliferative CMML, while according to WHO classification, 8 patients belonged to CMML-0, 9 patients to CMML-1 and 20 patients to CMML-2. At the time of diagnosis, the median white blood cell count was 32.84×10⁹/L, median hemoglobin (Hb) was 101 g/L, median platelet count was 65×10⁹/L, median absolute monocyte count was 9.53×10⁹//L, median absolute neutrophil count (ANC) was 11.29×10⁹//L and median lactate dehydrogenase (LDH) was 374 U/L. Cytogenetic abnormalities were found in 4 cases among the 31 patients who underwent karyotype analysis or fluorescence in situ hybridization detection. There were 12 patients who had analyzable results and gene mutations were identified in 11 cases, including ASXL1, NRAS, TET2, SRSF2 and RUNX1. Among the 6 patients who were treated with HMA and could be evaluated for efficacy, 2 patients achieved complete remission, 1 patient achieved partial remission and 2 patients achieved clinical benefit. Compared with the non-HMA treatment group, overall survival (OS) time was not significantly prolonged in the HMA treatment group. Univariate analysis showed that Hb<100 g/L, ANC≥12×10⁹/L, LDH≥250 U/L and peripheral blood (PB) blasts ≥5% were significantly associated with poor OS, while WHO classification CMML-2, Hb<100 g/L, ANC≥12×10⁹/L, LDH≥250 U/L and PB blasts≥5% were significantly associated with poor leukemia-free survival (LFS) (P<0.05). Multivariate analysis showed that ANC≥12×10⁹/L and PB blasts≥5% were significantly associated with poor OS and LFS (P<0.05). CONCLUSION CMML has high heterogeneity in clinical characteristics, genetic changes, prognosis and treatment response. HMA can not significantly improve the survival of CMML patients. ANC≥12×10⁹/L and PB blasts≥5% are independent prognostic factors of OS and LFS in patients with CMML.
Humans ; Aged ; Leukemia, Myelomonocytic, Chronic/genetics* ; Retrospective Studies ; In Situ Hybridization, Fluorescence ; Survival Analysis ; Prognosis

OBJECTIVE: To investigate the clinical characteristics, therapeutic response and prognosis of patients with plasma cell leukemia (PCL) and improve the understanding of this disease. METHODS: The clinical manifestations, laboratory tests and treatment response of 27 patients with plasma cell leukemia treated in The Second Hospital of Shanxi Medical University from December 2010 to August 2019 were analyzed retrospectively, and their clinical characteristics were summarized. Kaplan-Meier method was used for survival analysis. RESULTS: There were 18 cases of primary plasma cell leukemia (pPCL) and 9 cases of secondary plasma cell leukemia (sPCL). The male to female ratio was 1.7∶1. The median age was 62 years old. The first manifestations were bone pain, fatigue, fever, splenomegaly and bleeding, and a large number of plasma cell infiltration was observed in the morphological examination of peripheral blood and bone marrow cells. 13 cases were detected by immunotyping and all of them expressed CD38/CD138. 8 cases underwent karyotype analysis, and 3 cases were normal, clonal abnormalities occurred in 5 cases. FISH detection was performed in 12 cases, of which 8 cases were abnormal. In 17 cases of bortezomib based chemotherapy, the ovevall response rate was 52.9%, which was higher than that in the non-bortezomib group, but there was no significant difference between the two groups (P =0.242). The overall median survival time of 27 patients was 6.4 months, the median progression-free survival time was 3.5 months, and the median survival time of patients with pPCL and sPCL was 8.2 months and 2.4 months, respectively, the difference between the two groups was statistically significant (P =0.031). CONCLUSION PCL is highly invasive and has diverse clinical manifestations, and is not sensitive to traditional chemotherapy. The median survival time of patients with pPCL is relatively longer than that of patients with sPCL. The chemotherapy regimen based on bortezomib improves the treatment effectiveness and prolongs the survival time of PCL patients.
Male ; Female ; Humans ; Leukemia, Plasma Cell/diagnosis* ; Retrospective Studies ; Bortezomib/therapeutic use* ; Prognosis ; Survival Analysis

Objective: To examine the value of intravascular ultrasound (IVUS) for excimer laser ablation (ELA) combined with drug-coated balloon (DCB) in treating lower limb arteriosclerotic obliterans (ASO). Methods: As a prospective case series study, patients who underwent ELA combined with DCB for lower limb ASO with the guidance of IVUS from September 2021 to March 2022 at Department of Vascular Surgery, Zhongshan Hospital, Fudan University were enrolled prospectively. Lesion characteristics, procedure-related outcomes and complications were collected. The therapy outcomes were compared with baseline data by paired t test. Results: There were 8 males and 2 females, aged (72.0±5.9) years (range: 61 to 81 years). Of all the 11 lesions, there were 8 lesions in superficial femoral artery and 3 in popliteal artery. The lesion length was (7.0±2.4) cm (range: 3.2 to 9.8 cm). There were 4 chronic totally occlusion and 7 severe stenosis. All patients underwent the operation successfully. The technical success rate was 10/11. Bailout stenting was performed in one lesion because of flow-limiting dissection. Four lesions were grade 3 to 4 in peripheral artery calcium score system, and 9 lesions with calcification arc≥180°. Larger diameter drug-coated balloons were selected in 5 lesions after measurement of intravascular ultrasound. The follow-up time was (6.0±1.9) months (range: 3 to 9 months). The ankle-brachial index of the patient was significantly improved immediately after surgery (0.97±0.13 vs. 0.48±0.18, t=-7.60, P<0.01) and at 3 months after surgery (0.95±0.12 vs. 0.48±0.18, t=-7.17, P<0.01). The 3-month primary patency rate was 11/11, the target lesion reintervention was 0 and ulcer healing rate was 3/4. Conclusion: IVUS assisted ELA in the treatment of lower limb artery lesions is safe and effective in early stage.
Female ; Male ; Humans ; Laser Therapy ; Lower Extremity ; Ultrasonography ; Femoral Artery ; Ultrasonography, Interventional

OBJECTIVE To explore standardized evaluation process for clinical comprehensive evaluation of blood lipid- regulating drugs and perform rapid assessment of clinical comprehensive evaluation of blood lipid-regulating drugs with different mechanisms so as to provide reference for the drug catalogue selection and rational drug use of medical institutions. METHODS Referring to guidelines and consensus such as the guideline for the management of comprehensive clinical evaluation of drugs， the methods such as literature research， expert interviews， and Delphi expert consultation were used to establish a multi-dimensional and multi-criteria clinical comprehensive evaluation index system and quantitative scoring table for blood lipid-regulating drugs around the two main lines of technical evaluation and policy evaluation. Then 13 blood lipid-regulating drugs with different mechanisms in 21 third-grade class-A medical institutions from five provinces and regions of Northwest China were scored from both technical and policy dimensions to form a comprehensive evaluation result. RESULTS The clinical comprehensive evaluation index system and corresponding rapid evaluation quantitative scoring table were constructed for blood lipid-regulating drugs in the five northwest provinces and regions. The technicalevaluation section included 6 primary indicators， 13 secondary indicators， and 34 tertiary indicators， totaling 110 points. The policy evaluation section included 4 primary indicators and 6 secondary indicators， with a total score of 40 points （30 points for some drugs） and a total score of 150 points （or 140 points）. The scoring results showed that the highest score was atorvastatin， followed by rosuvastatin and simvastatin. CONCLUSIONS Statins are still the cornerstone of drug therapy for patients with dyslipidemia； the rapid evaluation quantitative scoring table constructed in this study is comprehensive， systematic and operable. The evaluation process in this study can provide empirical references for other groups to exploring the standardized path and quality control mechanism of clinical comprehensive evaluation of drugs.

Humans ; Prognosis ; Leukemia, Myeloid, Acute/genetics* ; Mutation ; Karyotype ; High-Throughput Nucleotide Sequencing